Insecticidal para-thiocarbamoylphenyl phosphorothioates

ABSTRACT

A PROCESS FOR CONTROLLING INSECT PESTS WHICH COMPRISES TREATING AN AREA INFESTED WITH THE SAME WITH AN EFFECTIVE AMOUNT OF A COMPOUND REPRESENTED BY THE FORMULA:   1-(R-P(=S)(-R1)-O-),2-Y,4-(H2N-C(=S)-)BENZENE   WHEREIN R REPRESENTS ALKOXY HAVING FROM 2-3 CARBON ATOMS; R1 REPRESENTS A LOWER ALKOXY FROM 1 TO 3 CARBON ATOMS, PHENYL, CHLORO- OR BROMO-SUBSITUTED (LOWER)ALKOXY OF FROM 1 TO 3 CARBON ATOMS OR DI(LOWER ALKYL)AMINO; AND Y IS HYDROGEN, CHLORO OR BROMO.

United States Patent 3,636,205 INSECTICIDAL PARA-THIOCARBAMOYL- PHENYL PHOSPHOROTHIOATES Bernard Miller, Amherst, and Howard Margulies, Stoneham, Mass., assignors to American Cyanamid' Company, Stamford, Conn.

No Drawing. Continuation-impart of application Ser. No. 524,496, Feb. 2, 1966, now Patent No. 3,480,697. This application Nov. 18, 1969, Ser. No. 877,864

Int. Cl. A0111 9/36 US. Cl. 42 4211 Claims ABSTRACT OF THE DISCLOSURE A process for controlling insect pests which comprises treating an area infested with the same with an effective amount of a compound represented by the formula:

wherein R represents alkoxy having from 23 carbon atoms; R represents a lower alkoxy from l'to 3 carbon atoms, phenyl, chloroor bromo-substituted (lower)- alkoxy of from 1 to 3 carbon atoms or di(lower alkyl)- amino; and Y is hydrogen, chloro or bromo.

This application is a continuation-in-part of applicants co-pending application, Ser. No. 524,496, filed Feb. 2, 1966, now US. Pat. No. 3,480,697, issued on Nov. 25, 1969.

This invention relates to a novel class of thiobenzamides, to a method for the preparation thereof and has as its principal object their use in compositions for controlling a variety of arachnids and insects. More particularly, the invention relates to a novel class of compounds of the formula: 1

R IS I wherein R represents alkoxy or halo-substituted alkoxy, having from 2 to 4 carbon atoms; R represents lower alkyl, lower alkoxy, phenyl, halo-substituted (lower)- alkoxy, mono(lower alkyl)amino, di(lower alkyl)amino; and Y is hydrogen or halo-substituent, such as fluorine, chlorine, bromine or iodine.

Illustrative of the compounds contemplated are:

In general, the compounds of the invention are prepared in a straightforwardmanner byreacting in approximately equimolar am unt s-, a -,p-hydrox-ythiob enzamide with either a thiophosphoryl halide or a thiophosphonyl halide in the presence of a base. The reaction may be graphically illustrated as follows:

wherein R, R and Y are as defined above and X is a halo-substituent, such as chloro or bromo.

The reaction may be carried out over a wide temperature range, as for instance, over the range of from about 0 C. to about 100 C., and in the presence of a variety of solvents, such as water; lower alcohols, such as ethanol or propanol; lower alkyl esters, such as ethyl acetate or butyl acetate; lower aliphatic ketones, such as methylisobutylketone, methylethylketone; glycols, such as ethylene glycol; as well as aromatic solvents, such as benzene. Although the reaction temperature and the solvent medium may be widely varied, the presence of a base is a prime requirement. A strong base will maximize the effectiveness of the reaction. Exemplary strong bases include: sodium methoxide, sodium hydroxide, potassium hydroxide, and potassium t-butoxide.

The compounds of the present invention may alternatively be obtained by the reaction between an 0,0- dialkyl-p-carbamoylphenyl phosphorothioate and phosphorus pentasulfide in equimolar amounts. The reaction may be graphically shown as follows:

where R and Y are defined hereinabove. The reaction is :advantageously carried out in inert solvents, such as benzene, toluene or chloroform.

The novel compounds above defined are unusually effective contact and systemic insecticides and arachnicides. It has also been noted that these novel compounds are exceedingly effective as a miticide against both the larvae and adult stages of the latter.

Application of the compounds of the invention for the purpose of pest control can be accomplished using conventional type formulations and equipment. The compounds may be formulated as Wettable powders, dusts, dust concentrates, emulsifiable concentrates and the like which are amenable to application with conventional spraying or dusting apparatus.

Wettable powder formulations are generally prepared by admixing from about 25% to 95% by Weight of active ingredient with finely ground clay, such as kaolin or attapulgite, either with or without a surface active agent, emulsifier or spreader-sticker. The latter is then dispersed in water for spray application.

Dusts and dust concentrates are similarly prepared using from about 5% to of active ingredient and from about to 5% of finely divided inert ingredients. These dusts are generally applied as such, or they may be further diluted with finely ground inert solids and then applied with conventional dusting apparatus.

Emulsifiable concentrates may be prepared by dissolving or dispersing the active ingredient in organic solvent, with or without emulsifying agents, surfactants or the like. Such formulations are then diluted with either water or an appropriate organic diluent prior to application.

The invention may be better understood by referring to the examples provided below which are to be taken as merely illustrative. Unless otherwise specified, parts are by weight.

EXAMPLE 1 Preparation of O-ethyl O-methyl O-p-thiocarbamoylphenyl phosphorothioate To a solution of 0.3 mole of potassium t-butoxide and 0.3 mole p-hydroxythiobenzamide in 250 ml. of t-butanol is added 0.3 mole of O-methyl O-ethyl chlorothiophosphate. The solution is allowed to stand for minutes and then poured into water, extracted with methylene chloride, the extract dried and the solvent evaporated under vacuum. The solid obtained is recrystallized from a petroleum ether-benzene mixture to yield 0.4 gram (5.0%) yellow solid, melting point 7072 C.

Analysis.-Calcd for C H PNS O (percent): C, 41.2; H, 4.85; N, 4.81; P, 10.63. Found (percent): C, 40.50; H, 4.75; N, 4.26; P, 10.58.

EXAMPLE 2 Preparation of O,-O-diethy1 O-p-thiocarbamoylphenyl phosphorothioate A solution of 5.1 grams (0.033 mole) p-hydroxythiobenzamide, 6.25 grams (0.033 mole) 0,0-diethyl chlorothiophosphate and 3.7 grams (0.033 mole) potassium t-butoxide in 300 ml. tert-butanol is stirred at room temperature overnight. The neutral solution is poured into Water, extracted with methylene chloride, the extract dried over MgSO and concentrated under vacuum to give a yellow solid. This is recrystallized from a benzene-petroleum ethyl mixture to give 4.8 grams (48%) (melting point 92 C.) yellow solid.

Analysis.Calcd for C H PNS O (percent): C, 43.3; H, 5.29; N, 4.59; S, 21.0; P, 10.16. Found (percent): C, 43.11; H, 5.08; N, 4.41; 8, 21.10; P, 10.21.

EXAMPLE 3 Preparation of O-2bromo-4-thiocarbamoylphenyl 0,0-diethyl phosphorothioate A solution of 0.13 mole of 3-bromo-4-hydroxythiobenzamide, 0.13 mole of potassium t-butoxide and 250 ml. of t-butanol is treated with 0.13 mole of 0,0-diethy1 chlorothiophosphate and permitted to stand for 15 minutes. The solution is then poured into water, extracted with methylene chloride, dried and the solvent evaporated under vacuum. The resulting yellow solid is recrystallized from a benzene-n-hexane mixture to yield 0.9 gram (18%) of product, whose melting point is 7173 C.

EXAMPLE 4 Preparation of O-2-chloro-4-thiocarbamoylphenyl 0,0-diethyl phosphorothioate A solution of 0.016 mole of potassium t-butoxide and 0.016 mole of 3-chloro-4-hydroxythiobenzamide in 250 ml. of t-butanol is treated with 0.016 mole of 0,0-diethyl chlorothiophosphate and permitted to stand for 15 minutes. The solution is then poured into water, extracted with methylene chloride, the extract dried over magnesium sulfate and concentrated under vacuum. The residue obtained as a yellow oil weighing 3.0 grams is then washed with n-hexane and run through a column of Florisil brand magnesium silicate to give 1.4 grams of material having an index of refraction (n equal to 1.6060.

AnaIysis.-Calcd for C H PNS O CI (percent): C, 38.9; H, 4.46; N, 4.13; S, 18.89; Cl, 10.43; P, 9.12. Found (percent): C, 38.82; H, 4.47; N, 4.09; S, 18.82; Cl, 10.61; P, 8.93.

4 EXAMPLE 5 Preparation of 0,0-bis(2-chloroethy1) O-p-thiocarbamoylphenyl phosphorothioate To a stirred solution of 250 m1. of t-butanol, 0.03 mole of p-hydroxythiobenzamide and 0.03 mole of potassium t-butoxide is added 0.03 mole of 0,0-di-2-chloroethyl phosphorochloridothioate. The mixture is allowed to stand for fifteen minutes, then admixed with water and extracted with methylene chloride. The methylene chloride phase is then dried and the solvent evaporated under vacuum to give the above product.

EXAMPLE 6 Preparation of O-ethyl O-p-thiocarbamoylphenyl N,N-dimethylphosphoramidothioate A stirred solution of 250 ml. of t-butanol, 0.03 mole of p-hydroxythiobenzamide and 0.03 mole of potassium t-butoxide is treated with 0.03 mole of O-ethyl dirnethylphosphoramidothioate. The mixture is permitted to stand for fifteen minutes, then poured into water, extracted with methylene chloride, the extract dried and concentrated under vacuum to give the above product.

EXAMPLE 7 Preparation of O-ethyl O-p-thiocarbamoylphenyl phenylphosphorothioate To a stirred solution of 0.03 mole of potassium tbutoxide and 0.03 mole of p-hydroxythiobenzamide in 250 ml. of t-butanol is added 0.03 mole of O-ethyl phenyl chlorothiophosphate. After standing for 15 minutes the solution is extracted with methylene chloride and the product run through a small column of magnesium silicate to yield a 3.7 gram fraction which solidified. This is recrystallized from a chloroform-n-hexane mixture to yield 1.5 grams of yellow solid having a melting point of 97-107 C.

Analysis.Calcd for C H PNS O (percent): C, 53.4; H, 4.78; N, 4.16; S, 19.00; P, 9.18. Found (percent): C, 53.21; H, 5.10; N, 4.16; S, 19.10; P, 9.21.

EXAMPLE 8 Preparation of 0,0-diisopropyl O-p-thiocarbarnoylphenyl phosphorothioate To a stirred solution of 3.65 grams (0.033 mole) of potassium t-butoxide in 150 m1. t-butanol at room temperature is added 5.0 grams (0.033 mole) of p-hydroxythiobenzamide. After 15 minutes, 7.1 grams (0.033 mole) 0,0-diisopropyl chlorothiophosphate is added and the mixture is refluxed for 6 hours and left standing overnight. The neutral solution is then poured into water, extracted with methylene chloride, the extract dried over magnesium sulfate and concentrated under vacuum to give 10 grams of viscous red oil which solidifies upon standing. Recrystallization from a benzene-n-hexane mixture gives 5.7 grams (54%) of yellow solid, melting point 112-114 C.

Analysis.Calcd for C H PNS Q, (percent): C, 46.9; -H, 6.04; N, 4.21; S, 19.25; P, 9.31. Found (percent): C, 46.84; H, 6.08; N, 4.11; S, 19.48; P, 9.10.

Similarly, the 0,0-di-n-butyl O-p-thiocarbamoylphenyl phosphorothioate is prepared by substituting for the 0,0- diisopropyl chlorothiophosphate, 0,0-di-n-butyl chlorothiophosphate and repeating the procedure of Example 8 above.

EXAMPLE 9 Preparation of 0,0-diethyl O-p-thiocarbamoylphenyl phosphorothioate 3.5 grams of 0,0-diethyl-p-carbamoylphenyl phosphorothioate is added to a vigorously stirred suspension of phosphorus pentasulfide (0.54 gram) in 100 m1. benzene. The mixture is refluxed for 15 minutes, poured into cold water, and the benzene layer dried over magnesium sulfate. Filtration and evaporation of the solvent left 3.6 grams of yellow solid. Recrystallization from benzenehexane gives 1.4 grams (38%) of solid, melting point 89-90" C., identical in IR spectrum with the product of Example 1.

The following examples are included to illustrate the preparation of novel thiobenzamide reactants.

EXAMPLE Preparation of p-hydroxythiobenzamide To a saturated solution of hydrogen bromide in 350 ml. of dimethyl formamide is added 100 g. of p-hydroxybenzonitrile and 126 g. of thioacetamide. This mixture is heated on a steam bath at 100 C. for minutes and then the dimethyl formamide distilled off at 1520 mm. and 88-98 C. When distillation is complete, the acidic solution is neutralized with one liter of dilute sodium bicarbonate and the hot solution is filtered and the filtrate permitted to cool. On cooling the solid precipitates, is separated from the solution and recrystallized from 1500 ml. of water, then dried under vacuum, recovered and identified above and has a melting point of 197199 C.

EXAMPLE 11 Preparation of 3-bromo-4-hydroxythiobenzamide A solution of acetic acid containing 0.3 mole of phydroxybenzonitrile and 0.5 mole of sodium acetate is treated with 0.3 mole of bromine to yield a mixture of 3-bromo-4-hydroxybenzonitrile and 2,3-di-bromo-4-hydroxybenzonitrile. The mixed product is recrystallized from iso-propanol, then treated with water and recrystallized again from benzene to yield the monobrominated product having a melting point of 152154 C. The 3- bromo-4-hydroxybenzonitrile is then mixed with 80 g. of pyridine and g. of triethylamine. Hydrogen sulfide gas is bubbled into this mixture and the mixture poured into water. This is acidified with aqueous hydrogen chloride, extracted with ethyl acetate and the extract dried over magnesium sulfate. After concentration of the residue, the yellow solid obtained is treated with toluene and recovered therefrom. This product has a melting point of l69171 C.

In repeating the above procedure, the corresponding 3- chloroor 3-iodo-4-hydroxythiobenzamide can be prepared readily by substituting either chlorine or iodine for the bromine.

The following examples illustrate the utility of the phenylthioamides of the present invention.

EXAMPLE 12 Contact miticidal activity of the compounds of the instant invention is compared with a lower homologue, namely, 0,0-dimethyl O-p-thiocarbamoylphenyl phosphorothioate by employing the following procedure: Sieva lima bean plants are infested about five hours before testing using about 200 adult mites per leaf. The infested leaves are dipped in test solutions made up in .01% concentration of active compound or ingredient in 65 acetone and water. After the leaves of the plants are dipped, they are placed in a hood to dry and when dry held for two days in a constant temperature and humidity room at 80 F., 60% RH. Following the two-day holding period, the adult mite mortality count is determined by examining the plants under a 10x binocularscope.

Summarized results of the tests are provided in Table I following the examples.

EXAMPLE 13 Systemic miticidal activity of the compounds of the im vention is demonstrated by the following tests in which the activity of the 0,0-dimetl1yl O-p-thiocarbamoylphenyl phosphorothioate, a lower homolog, is compared with the activity of the novel substituted, tabularized analogs. In the tests, the individual compounds are prepared as 100 ppm. emulsions in acetone and water. These test emulsions are placed in separate 2-ounce bottles. Sieva lima bean plants, cut off just above soil level, are then inserted in the bottles containing the test solutions. The bottles are arranged in ventilated boxes with the leaves extending outside of the boxes to assure that the fumes from the compounds are drawn out through the boxes rather than rising to affect the test plants. About 50 adult mites are placed on one leaf of each plant and permitted to remain there for three days. Following the holding period, the leaves are examined and the mortality counts made.

The systemic activity of the compounds is summarized as shown in Table I below.

EXAMPLE 14 The effectiveness and vast superiority of the compounds of the instant invention over the known 0,0-dimethyl O-p-thiocarbamoylphenyl phosphorothioate in controlling southern armyworms (Prodenia eridania Cram.) is dramatically demonstrated by the following tests wherein the compounds are individually prepared as 0.1% solutions of test compound in 65% acetone/ 35% water mixture. Sieva lima bean plants are dipped in the test solutions and set in the hood to dry. When dry, they are placed in four-inch petri dishes on a moist filter paper and ten third-instar larvae are added to each test plate. The plates are covered and maintained at about F., 60% RH. for two days. Following the holding period, mortality counts are made and estimates of amount of feeding observed and recorded. From the data provided in Table II, it is evident that the compounds are highly-effective for controlling armyworms.

EXAMPLE 15 The systemic activity and superiority of the compounds of the instant invention over the 0,0-dimethyl O-p-thiocarbamoylphenyl phosphorothioate for controlling southern armyworms is demonstrated by the following tests using ppm. emulsions prepared as in Example 13 above. As in the previous example, sieva lima bean plants cut off just above the soil line are inserted in the bottles containing test emulsion. The bottles are then placed in boxes and fumes withdrawn from the box in order that they do not contact the leaves. The bottles are permitted to remain in the boxes for three days, then removed and the leaves from said plants placed in petri dishes on a moist filter paper. Ten third-instar southern armyworm larvae are then added to each test plate and permitted to remain there for an additional three days. At the end of this time the dishes are examined and the mortality count made. Systemic control of southern armyworm with the compounds of the instant invention is evidenced by the atoms, phenyl, chloroor bromo-substituted (lower) alkoxy of from 1 to 3 carbon atoms or di(10wer alkyl) amino; and Y is hydrogen, chloro or bromo.

2. The method according to claim 1 in which the comresults of these tests provided in Table II. 5 pound is O-ethyl O-methyl O-p-thiocarbamoylphenyl phosphorothioate. EXAMPLE 16 3. The method according to claim 1 in which the com- The significance of the ethyl substitution in the cornpound is O-2-brom0-4-thiocarbamoylphenyl 0,0-diethyl pounds of the invention for mosquito larvae (Anopheles phosphorothioate. quadrimaculatus Say) control is shown by the following 4. The method according to claim 1 in which the comtests wherein groups of 25 larvae of the common malaria pound is 0,0-diethyl Op-thiocarbamoylphenyl phosmosquito are transferred with a medicine dropper to a phorothioate. 50 ml. beaker containing 25 ml. of water. The test com- 5. The method according to claim 4 in which the insect pound is formulated as an emulsion containing an emulpests are southern armyworms. sifier, acetone and water and added to the Water in suf- 6. The method according to claim 1 in which the insect ficient amount to provide 0.1 ppm. of candidate compests are mites. pound when admixed with m1. of water containing the 7. An insecticidal composition comprising an inert inmosquito larvae. Mortality counts are made after 24 secticidal carrier and an insecticidally effective amount of hours at 80 F. The results are given in Table II below. the compound of claim 1.

TABLE II Armyworm Arrnyworms, systemic, Mosquito, Structure 100 p.p.m. 0.1 p.p.m.

i i 64 (CHaO)zPO-CNHz Br 70 30 98 i it (G2H 0)2P-0 -CNH2 Cl 100 100 100 i i (C2H5O)2-PO-CNH2 t (C2H5O)gPOCNHz 100 100 CHaQ iS HS POCNH2 100 100 C2H5O What is claimed is:

8. The composition of claim 7 in which the compound 1, A method for controlling insect pests which com- 50 is O-ethyl O-methyl O-p-thiocarbamoylphenyl phosphoroprises treating an area infested with the same with an insecticidally effective amount of a compound having the wherein R represents alkoxy having from 2-3 carbon atoms; R represents lower alkoxy of from 1 to 3 carbon 60 thioate.

9. The composition according to claim 7 in which the compound is 0,0-diethyl O-p-thiocarbamoyiphenyl phosphorothioate.

10. The composition according to claim 7 in which the compound is O-2-bromo-4-thiocarbamoylphenyl 0,0-diethyl phosphorothioate.

No references cited. 

